title: Toll-like receptor 9 is required for chronic stress-induced immune suppression.
abstract: OBJECTIVE
  Mental and physical stress can suppress the immune system in both humans and animals. The mechanism by which stress affects immune responses, however, remains poorly defined. Toll-like receptors (TLRs) play a key role in modulating immune responses and cell survival. The mechanisms by which TLRs modulate chronic stress are largely unexplored.
  
  
  METHODS
  Six- to 8-week-old male mice were subjected to chronic 12-hour daily physical restraint stress. Apoptotic cells were determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. We examined cytokine levels by enzyme-linked immunosorbent Assay (ELISA). The expression of CYP11A1 was determined by quantitative real-time RT-PCR.
  
  
  RESULTS
  TLR9-deficient mice were resistant to chronic stress-induced lymphocyte apoptosis. In addition, in TLR9 knockout (KO) mice, chronic stress-induced upregulation of corticosterone levels was significantly decreased. Notably, lymphocytes from both TLR9 KO and wild-type mice were similarly sensitive to corticosteroid-induced cell apoptosis. Moreover, TLR9 deficiency blocked the chronic stress-induced imbalance in T helper (Th) 1 and Th2 cytokine levels.
  
  
  CONCLUSIONS
  Taken together, our findings reveal that TLR9 plays an essential role in chronic stress-induced immune suppression.
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, Tenn., USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Michael
authors.initials: M
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Tan
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Caudle
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D007108:Immune Tolerance / Q000235:genetics* / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012149:Restraint, Physical / Q000009:adverse effects; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000502:physiology*
chemical_list: D016207:Cytokines; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone